. The goal of this program is to use controlled release technology to develop improved penetration enhancers for use in transdermal or topical drug-delivery systems. Transdermal drug delivery offers several advantages over other routes of drug administration, but has been successfully commercialized for only a limited number of drugs. The primary factor responsible for this limited use of transdermal drug delivery is the low transdermal flux of most drugs. Although penetration enhancers have been identified that increase the transdermal penetration of specific drugs, the utility of such enhancers is limited by rapid clearance from the application site through transdermal permeation and/or evaporation. It is stated that in Phase I of this program, the feasibility of controlled-release penetration enhancers to increase the drug flux was demonstrated for a model drug/enhancer combination. Both the quantity of drug delivered and the duration of delivery were significantly increased over the quantity and duration observed without controlled release. The goal in Phase II is to demonstrate the utility of this approach for drugs and enhancers that are representative of a wide range of potential transdermal products.